Ammonium Hydroxide → 4-Cyano-3-(2,4-dichlorophenyl)-5-(2-(fluoromethyl)morpholino)thiophene-2-carboxamide

HRID 1926610Notes

Reaction equation

HRID 1926610 reaction equation
[C:1]([C:3]1[C:4]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:20]=2[Cl:26])=[C:5]([C:16]([OH:18])=O)[S:6][C:7]=1[N:8]1[CH2:13][CH2:12][O:11][CH:10]([CH2:14][F:15])[CH2:9]1)#[N:2].[OH-].[NH4+].CC[N:31]=C=NCCCN(C)C>C(Cl)Cl>[C:1]([C:3]1[C:4]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:20]=2[Cl:26])=[C:5]([C:16]([NH2:31])=[O:18])[S:6][C:7]=1[N:8]1[CH2:13][CH2:12][O:11][CH:10]([CH2:14][F:15])[CH2:9]1)#[N:2]

Participants

5

Reactant 3

HCID 14923Ammonium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 670728204-Cyano-3-(2,4-dichlorophenyl)-5-(2-(fluoromethyl)morpholino)thiophene-2-carboxylic acid

Product 1

HCID 670728904-Cyano-3-(2,4-dichlorophenyl)-5-(2-(fluoromethyl)morpholino)thiophene-2-carboxamideYield 56%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 4-cyano-3-(2,4-dichlorophenyl)-5-(2-(fluoromethyl)morpholino)thiophene-2-carboxylic acid (68.0 mg, 0.000164 mol), 33% ammonium hydroxide (33:67, ammonia:water, 0.1416 mL), EDCI (94.2 mg, 0.000491 mol) and 1-HOBT (66.4 mg, 0.000491 mol) in DCM (7 mL, 0.1 mol) was stirred at it overnight. The reaction mixture was diluted with DCM and washed with water, the organic layer was dried and purified by column chloromatography to afford 4-cyano-3-(2,4-dichlorophenyl)-5-(2-(fluoromethyl)morpholino)thiophene-2-carboxamide (38 mg, 56%). LCMS: (FA) ES+ 414, ES− 412; 1H NMR (400 MHz, d1-chloroform) δ: 7.59 (d, 1H), 7.42 (dd, 1H), 7.31 (d, 1H), 6.00 (s, 1H), 4.50 (dd, 2H), 4.12-4.08 (m, 2H), 4.00-3.78 (m, 4H), 3.36-3.25 (m, 1H), 3.22-3.15 (m, 1H)

Workup

  1. washwashed with water
  2. customthe organic layer was dried
  3. custompurified by column chloromatography

Sources & evidence

ORD record
ord-3092be222f544079ba3194c6aff70de1
Source dataset
uspto-grants-2012_05
Patent number
US08183240B2

Reaction notes

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